(5-(4-fluorophenoxy)-2-furyl)acetylene | 141580-63-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (5-(4-fluorophenoxy)-2-furyl)acetylene
• 英文别名: 5-(4-fluorophenoxy)-2-furylethyne；2-[5-(4-fluorophenoxy)-2-furyl]-ethyne；2-[5-(4-fluorophenoxy)-furan-2-yl]-ethyne；2-ethynyl-5-(4-fluorophenoxy)furan
• CAS: 141580-63-4
• 化学式: C₁₂H₇FO₂
• 分子量: 202.185
• InChiKey: AWODTHBWBBOGFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  22.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5-(4-fluorophenoxy)-2-furyl)acetylene 在 偶氮二甲酸二异丙酯 、 氨 、 三苯基膦 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 N-hydroxy-N-[3-(5-(4-fluorophenoxy)-furan-2-yl)-2-propynyl]urea
  参考文献：
  名称：

  Preparation of (R)-(+)-N-[3-[5-[(4-Fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (ABT-761), a second-generation 5-lipoxygenase inhibitor.

  摘要：

  Structure-activity optimization of inhibitory potency and duration of action of N-hydroxyurea containing 5-lipoxygenase inhibitors was conducted. The lipophilic heteroaryl template and the link group connnecting the template to the N-hydroxyurea pharmacophore were modified. Inhibition of 5-lipoxygenase was evaluated in vitro in a human whole blood assay. An in vitro assay using liver microsomes from monkey was used to evaluate congeners for comparative rates of glucuronidation. (3-Heteroaryl-1-methyl-2-propynyl)-N-hydroxyureas were found to be more resistant to in vitro glucuronidation. The promising inhibitor N-[3-[5-(4-fluorophenoxy)2-furyl]-1-methyl-2-propynyl]-N-hydroxyurea (6) was found to have stereoselective glucuronidation in monkey and man. The R enantiomer 7 provided longer duration of inhibition as evaluated by an ex vivo whole blood assay. Further optimization of the lipophilic template led to the discovery of (R)-(+)-N-[3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (11) with more effective and prolonged inhibition of leukotriene biosynthesis than zileuton (1) and 7 in monkey and man. The optimized 5-lipoxygenase inhibitor 11 was selected for development as an investigational drug for leukotriene-mediated disorders.

  DOI：

  10.1021/jm00024a004
• 作为产物：
  描述：

  5-硝基糠醛 在 正丁基锂 、 sodium hydride 、 三苯基膦 、 锌 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.0h， 生成 (5-(4-fluorophenoxy)-2-furyl)acetylene
  参考文献：
  名称：

  Preparation of (R)-(+)-N-[3-[5-[(4-Fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (ABT-761), a second-generation 5-lipoxygenase inhibitor.

  摘要：

  Structure-activity optimization of inhibitory potency and duration of action of N-hydroxyurea containing 5-lipoxygenase inhibitors was conducted. The lipophilic heteroaryl template and the link group connnecting the template to the N-hydroxyurea pharmacophore were modified. Inhibition of 5-lipoxygenase was evaluated in vitro in a human whole blood assay. An in vitro assay using liver microsomes from monkey was used to evaluate congeners for comparative rates of glucuronidation. (3-Heteroaryl-1-methyl-2-propynyl)-N-hydroxyureas were found to be more resistant to in vitro glucuronidation. The promising inhibitor N-[3-[5-(4-fluorophenoxy)2-furyl]-1-methyl-2-propynyl]-N-hydroxyurea (6) was found to have stereoselective glucuronidation in monkey and man. The R enantiomer 7 provided longer duration of inhibition as evaluated by an ex vivo whole blood assay. Further optimization of the lipophilic template led to the discovery of (R)-(+)-N-[3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (11) with more effective and prolonged inhibition of leukotriene biosynthesis than zileuton (1) and 7 in monkey and man. The optimized 5-lipoxygenase inhibitor 11 was selected for development as an investigational drug for leukotriene-mediated disorders.

  DOI：

  10.1021/jm00024a004

文献信息

• Asymmetric synthesis of (R)-N-3-butyn-2-yl-N-hydroxyurea, a key intermediate for 5-lipoxygenase inhibitors
  作者：Teodozyj Kolasa、Andrew O. Stewart、Clint D.W. Brooks

  DOI：10.1016/0957-4166(96)00068-7

  日期：1996.3

  An efficient asymmetric synthesis of (R)-N-3-butyn-2-yl-N-hydroxyurea from crotyl alcohol is described. The process involves asymmetric Sharpless epoxidation to establish the stereochemistry, formation of (S)-3-butynol and hydroxyl substitution with inversion by the masked N-hydroxyurea reagent N,O-bis(phenoxycarbonyl)hydroxylamine in a Mitsunobu reaction.

  描述了从巴豆醇有效地不对称合成（R）-N -3-丁炔-2-基-N-羟基脲。该方法涉及不对称的Sharpless环氧化，以建立立体化学，形成（S）-3-丁炔醇，并通过Mitsunobu反应中被掩蔽的N-羟基脲试剂N，O-双（苯氧基羰基）羟胺转化而进行羟基取代。
• Acetylene derivatives having lipoxygenase inhibitory activity
  申请人：Abbott Laboratories

  公开号：US05476873A1

  公开（公告）日：1995-12-19

  Compounds of the structure ##STR1## where p and q are zero or one, but cannot both be the same, M is a pharmaceutically acceptable cation or a metabolically cleavable group, B is a valence bond or a straight or branched alkylene group, R is alkyl, cycloalkyl or --NR.sup.1 R.sup.2, where R.sup.1 and R.sup.2 are hydrogen, alkyl, cycloalkyl or alkanoyl, and A is optionally substituted carbocyclic aryl, furyl, benzo[b]furyl, thienyl, or benzo[b]thienyl are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

  结构式为## STR1 ##的化合物，其中p和q为零或一，但不能同时相同，M是药学上可接受的阳离子或代谢可裂解基团，B是价键或直链或支链烷基，R是烷基，环烷基或--NR.sup.1 R.sup.2，其中R.sup.1和R.sup.2是氢，烷基，环烷基或烷酰基，而A是可选的取代的碳环芳基，呋喃基，苯并[b]呋喃基，噻吩基或苯并[b]噻吩基是脂氧合酶酶的强力抑制剂，从而抑制白三烯的生物合成。这些化合物在治疗或改善过敏和炎症疾病状态方面有用。
• [EN] ACETYLENE DERIVATIVES HAVING LIPOXYGENASE INHIBITORY ACTIVITY
  申请人：ABBOTT LABORATORIES

  公开号：WO1992001682A1

  公开（公告）日：1992-02-06

  (EN) Compounds of the structure (I) where p and q are zero or one, but cannot both be the same, M is a pharmaceutically acceptable cation or a metabolically cleavable group, B is a valence bond or a straight or branched alkylene group, R is alkyl, cycloalkyl or -NR1R2, where R1 and R2 are hydrogen, alkyl, cycloalkyl or alkanoyl, and A is optionally substituted carbocyclic aryl, furyl, benzol[b]furyl, thienyl, or benzol[b]thienyl are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.(FR) L'invention concerne des composés ayant la formule (I) dans laquelle p et q sont égaux à zéro ou un, mais sont différents l'un de l'autre, M est un cation pharmaceutiquement acceptable ou un groupe clivable par le métabolisme, B est une liaison de valence ou un groupe alkylène linéaire ou ramifié, R est alkyle, cycloalkyle ou -NR1R2, où R1 et R2 sont hydrogène, alkyle, cycloalkyle ou alcanoyle, et A est aryle, furyle, benzo[b]furyle, thiényle ou benzo[b]thiényle carbocyclique substitué ou non; ces composés sont de puissants inhibiteurs des enzymes de lipoxygénase et par conséquent ils inhibent la biosynthèse des leukotriènes. Les composés de cette invention sont utiles pour traiter ou pour améliorer les états pathologiques allergiques et inflammatoires.

  化合物的结构为（I），其中p和q为零或一，但不能同时相同，M是一种药物可接受的阳离子或代谢可裂解的基团，B是一个价键或直链或支链烷基基团，R是烷基，环烷基或-NR1R2，其中R1和R2是氢，烷基，环烷基或脂肪酰基，A是可选的取代的碳环芳基，呋喃基，苯并[b]呋喃基，噻吩基或苯并[b]噻吩基，是脂氧合酶酶的有效抑制剂，从而抑制白三烯的生物合成。这些化合物在治疗或改善过敏性和炎症疾病状态方面非常有用。
• Lipoxygenase and cyclooxygenase inhibiting compounds
  申请人：Abbott Laboratories

  公开号：US05516789A1

  公开（公告）日：1996-05-14

  Compounds having the structure ##STR1## or a pharmaceutically acceptable salt thereof have activity as inhibitors of cylooxygenase and 5-lipoxygenase, reduce the biosynthesis of leukotrienes B.sub.4, C.sub.4, D.sub.4, and E.sub.4 and cylooxygenase products such as prostaglandins and thromboxane and are useful in the treatment of inflammatory and allergic disease states. The compounds have the structure indicated above wherein A is selected from (a) optinally substituted carbocyclic aryl, (b) optinally substituted furyl, (c) optinally substituted benzo[b]furyl, (d) optinally substituted thienyl, (e) optinally substituted pyridyloxy, (f) optinally substituted pyridylalkyl, (g) optinally substituted benzo[b]thienyl, (h) optinally substituted pyridyl, (i) optinally substituted quinolyl, and (j) optinally substituted indolyl; X is selected from (a) optionally substituted alkyl, (b) optinally substituted alkenyl, and (c) optinally substituted alkynyl; R.sup.1 and R.sup.2 are independently selected from hydrogen, hydroxy, and alkyl; and Z is a residue of a non-steroidal anti-inflammatory drug of the general formula Z--COOH.

  具有结构##STR1##或其药学上可接受的盐具有抑制环氧合酶和5-脂氧合酶的活性，减少白三烯B.sub.4、C.sub.4、D.sub.4和E.sub.4以及前列腺素和血栓素等环氧合酶产物的生物合成，并可用于治疗炎症和过敏性疾病状态。其中上述化合物具有上述结构，其中A选自(a)可选取的取代的碳环芳基，(b)可选取的取代的呋喃基，(c)可选取的取代的苯并[b]呋喃基，(d)可选取的取代的噻吩基，(e)可选取的取代的吡啶氧基，(f)可选取的取代的吡啶基烷基，(g)可选取的取代的苯并[b]噻吩基，(h)可选取的取代的吡啶基，(i)可选取的取代的喹啉基，以及(j)可选取的取代的吲哚基；X选自(a)可选取的取代的烷基，(b)可选取的取代的烯基，以及(c)可选取的取代的炔基；R.sup.1和R.sup.2分别选自氢、羟基和烷基；而Z是非甾体抗炎药的残基，其一般式为Z--COOH。
• J. Med. Chem. 1995, 38, 4768-4775
  作者：

  DOI：——

  日期：——